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. 2025 Mar;100(3):402-407.
doi: 10.1002/ajh.27576. Epub 2025 Jan 5.

Hyper-CVAD and Sequential Blinatumomab Without and With Inotuzumab in Young Adults With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia

Hagop Kantarjian  1 , Nicholas J Short  1 , Nitin Jain  1 , Fadi G Haddad  1 , Tapan Kadia  1 , Musa Yilmaz  1 , Alessandra Ferrajoli  1 , Koji Sasaki  1 , Yesid Alvarado  1 , Naveen Pemmaraju  1 , Jayastu Senapati  1 , Rebecca Garris  1 , Farhad Ravandi  1 , Elias Jabbour  1
Affiliations

Hyper-CVAD and Sequential Blinatumomab Without and With Inotuzumab in Young Adults With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia

Hagop Kantarjian et al. Am J Hematol. 2025 Mar.

Abstract

Adding inotuzumab ozogamicin (InO) to hyper-CVAD and blinatumomab may improve outcomes in newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL). Patients with newly diagnosed B-ALL received up to four cycles of hyper-CVAD followed by four cycles of blinatumomab. Beginning with patient #39, InO 0.3 mg/m2 was added on Days 1 and 8 to two cycles of high-dose methotrexate and cytarabine, and two cycles of blinatumomab. The primary endpoint was the relapse-free survival (RFS) rate. Seventy-five patients were treated (median age of 33 years; range, 18-59), of whom 37 (49%) received hyper-CVAD with blinatumomab and InO (cohort 2). Measurable residual disease (MRD) negativity by next-generation sequencing (sensitivity: 1 × 10-6) was achieved in 79% of patients in cohort 2. The median follow-up was 44 months (range, 13-90) overall, and 26 months (range, 8-39) in cohort 2. For the entire cohort, the estimated 3-year RFS rate was 82% and the 3-year overall survival rate was 90%. These rates were 90% versus 74% (p = 0.06) and 100% versus 82% (p = 0.01) in patients who did or did not receive InO, respectively. No sinusoidal obstruction syndrome was observed. In summary, hyper-CVAD with blinatumomab and InO improved the outcomes of patients with newly diagnosed B-ALL.

Keywords: ALL; chemotherapy; frontline; immunotherapy; survival.

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Conflict of interest statement

Conflict-of-interest disclosure

The other authors report no relevant conflicts of interest.

Figures

Figure 1.
Figure 1.
Consort Diagram
Figure 2.
Figure 2.
(A) Relapse-free and Overall survival for the totality of patients treated in the two cohorts, (B) Overall survival by cohort, and (C) Relapse-free survival by cohort
Figure 2.
Figure 2.
(A) Relapse-free and Overall survival for the totality of patients treated in the two cohorts, (B) Overall survival by cohort, and (C) Relapse-free survival by cohort
Figure 2.
Figure 2.
(A) Relapse-free and Overall survival for the totality of patients treated in the two cohorts, (B) Overall survival by cohort, and (C) Relapse-free survival by cohort
See this image and copyright information in PMC

References

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